Emerging therapeutics for rheumatoid arthritis.
Therapeutics options for rheumatoid arthritis (RA) have increased tremendously in the past decade with the introduction of biological agents in 1999. Several different cellular and cytokine targets have been identified, with specific inhibitors now approved to treat RA, including the tumor necrosis factor (TNF) antagonists (adalimumab, etanercept, infliximab), an interleukin 1 (IL1) antagonist (anakinra), an inhibitor of T cell co-stimulation (abatacept), and a selective depleter of B cells (rituximab). As research has progressed, additional promising targets have been identified. Results from RA studies using several new agents have been reported in the last year. Some of these compounds are similar to agents already available, with additional TNF inhibitors (certolizumab pegol, golimumab) and agents targeting CD20 (ocrelizumab, ofatumumab, TRU-015) in development. Other agents are directed toward new cytokine targets, including IL-6 (tocilizumab), and lymphotoxin pathways (briobacept), as well as other B-cell targets, to include BLyS and APRIL (belimumab, atacicept). Additional small molecule therapies have been studied that are directed against intracellular kinases, including JAK-3 and Syk. This article provides a brief update of data from selected clinical trials in RA, highlighting efficacy, and mechanism-based safety concerns.
Bingham
Clifton O
CO
John Hopkins University, Baltimore, MD, USA. clifton.bingham@jhmi.edu
D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors; D015507:Drugs, Investigational / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D018501:Antirheumatic Agents; D016207:Cytokines; D015507:Drugs, Investigational; D007155:Immunologic Factors; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha